Recombinant human interleukin-1 receptor antagonist in the treatment of steroid-resistant graft-versus-host disease

Autor: J H, Antin, H J, Weinstein, E C, Guinan, P, McCarthy, B E, Bierer, D G, Gilliland, S K, Parsons, K K, Ballen, I J, Rimm, G, Falzarano
Rok vydání: 1994
Předmět:
Zdroj: Blood. 84:1342-1348
ISSN: 1528-0020
0006-4971
DOI: 10.1182/blood.v84.4.1342.bloodjournal8441342
Popis: Acute graft-versus-host disease (GVHD) that is resistant to therapy is a highly lethal complication of marrow transplantation. Inflammatory cytokines such as interleukin-1 (IL-1) may be critical mediators of this process. If so, specific inhibition of IL-1 activity with recombinant human IL-1 receptor antagonist (IL-1Ra), a naturally occurring competitive inhibitor of IL-1, may ameliorate acute GVHD. We performed an open-label, phase I/II trial to evaluate the safety and efficacy of IL-1Ra in 17 patients with steroid-resistant GVHD. The IL- 1Ra was administered as a 24-hour continuous infusion over 7 days. The dose was escalated in cohorts of patients from 400 to 3,200 mg/d. Acute GVHD was evaluated in each affected organ and as an overall grade. Stage-specific improvement of acute GVHD occurred in the skin (8 of 14, 57%), gut (9 of 11, 82%), and liver (2 of 11, 18%). Overall, acute GVHD improved by at least one grade in 10 of 16 (63%) patients. Response to therapy was associated with a reduction of tumor necrosis factor-alpha (TNF-alpha) mRNA levels in blood mononuclear cells (P = .001). The only toxicity attributable to IL-1Ra was reversible transaminase elevation in two patients. Inhibition of IL-1 activity with IL-1Ra is safe and has demonstrable efficacy in acute GVHD that failed to respond to conventional treatment. These data provide further evidence that IL-1 is a mediator of GVHD.
Databáze: OpenAIRE
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